Tenecteplase for Treatment of Acute Ischemic Stroke

•Background on TNK

•Published studies of TNK in Stroke

•Ongoing studies of TNK in Stroke

•AHA/ASA Guidelines relative to TNK

•Mission and New Hanover experience

•Impact of the COVID pandemic on thrombolytic treatment of stroke

Alteplase

Tenecteplase

Andrew W. Asimos, MD

Medical Director, Carolinas Stroke Network

Atrium Health

Professor, Department of Emergency Medicine

Carolinas Medical Center

Charlotte, NC

Tenecteplase

•Third-generation, genetically modified version of rt-PA•Longer half life - given as a single bolus

•Greater fibrin specificity - theoretical advantage of reduced risk of hemorrhage

•Greater resistance to its endogenous inhibitor

•Workflow advantages, with potential time and money savings•Especially for interfacility transfer for thrombectomy

•Not FDA approved for use in stroke•Does not currently have a high LOR for acute stroke thrombolysis in the most recent AHA/ASA guideline

Two Published Meta-analyses of Tenecteplase versus Alteplasefor Management of Acute Ischemic Stroke

Tenecteplase versus Alteplase for Management of Acute Ischemic Stroke:Characteristics of the Included Randomized Clinical Trials

Kheiri, B. et al. J Thromb Thrombolysis 2018;46:440–450. https://doi.org/10.1007/s11239-018-1721-3

Tenecteplase versus Alteplase for Management of Acute Ischemic Stroke:Meta-analysis of Randomized Clinical Trials

Kheiri, B. et al. J Thromb Thrombolysis 2018;46:440–450. https://doi.org/10.1007/s11239-018-1721-3

Forest Plots of the Efficacy Outcomes: TNK vs Alteplase

Kheiri, B. et al. J Thromb Thrombolysis 2018;46:440–450. https://doi.org/10.1007/s11239-018-1721-3

Forest Plots of the Safety Outcomes: TNK vs Alteplase

Kheiri, B. et al. J Thromb Thrombolysis 2018;46:440–450. https://doi.org/10.1007/s11239-018-1721-3

Tenecteplase vs Alteplase

•Compared with alteplase, higher rates of recanalization and early neurological improvement with TNK

•TNK is not associated with significant differences in safety compared with alteplase

•TNK 0.25 mg/kg is associated with better imaging-based outcomes and higher levels of function than alteplase, with no increased risk of intracerebral bleeding or mortality

Kheiri, B. et al. J Thromb Thrombolysis 2018;46:440–450. https://doi.org/10.1007/s11239-018-1721-3

Campbell BCV et al. JAMA Published online February 20, 2020. doi:10.1001/jama.2020.1511

Distribution of 90-day mRS in pooled analysis of the EXTEND-IA TNK trials

Campbell BCV et al. JAMA Supplementary Online Content Published online February 20, 2020.

doi:10.1001/jama.2020.1511

TWIST ATTEST-2 TASTE-2 TIMELESS TEMPO-2 NORTEST-2 TASTEa

Countries Europe UK Australia US, Canada Multinational Norway Australia

Target Enroll # 500 1,870 1,124 456 1,124 1.342 80

% Target enrolled(as of 8/1/20)

100% ~49% ~42% ~38% ~37% ~1% ?

Time window ≤4.5 hrFrom

wake-up

≤4.5 hr ≤4.5 hr 4.5 - 24 hr ≤12 hr,NIHSS <6,

ASPECTS >7

≤4.5 hr from LKWor awakening,

NIHSS >5

≤4.5 hr,Tx in MSU

Imaging UECT UECT CTP/MRI CTP/MRI CTA/MRA/CTP/MRP

UECT,FLAIR-DWI

UECT

TNK dose(s) 0.25 vsstandard tx

0.25 vs tPA 0.25 vs tPA 0.25 vs placebo

0.25 vs antiplatelet*

0.40 vs tPA 0.25 vs tPA

LVO Not required ICA, M1, M2 MCA, ACA,PCA, VB

Allowed Not required

Endovascular Tx Prohibited Allowed Prohibited Allowed

Outcome mRS at 3 mo mRS at 3 mo mRS at 3 mo mRS at 3 mo mRS at 3 mo mRS at 3 mo CTP lesion vol

Ongoing Trials of TNK in Acute Ischemic Stroke

* Planned thrombolysis with IV tPA excluded